Fig. 1: SAR study of glabridin and subsequent structural modifications improve in vivo weight loss effect and chemical stability of the structural analogs.

a Schematic of the development of HSG4112 from glabridin. HFD-induced obese mice (n = 4 for all obese groups and n = 2 for the vehicle group) were orally administered with 150 mg kg⁻¹ of respective glabridin derivatives for 4–6 weeks in b hydrogenation, c etherification, and d chain elongation steps. Data represent mean only, without statistical analysis, due to low sample size specifically employed for the purpose of screening. e HFD-induced obese mice (n = 5) were orally administered with 50 mg kg⁻¹ of (R)-, (S)-, or racemic HSG4112 for 6 weeks for the enantiomerization step. Data represent mean ± SEM. Two-way ANOVA with Dunnett’s multiple comparison test was performed; *p < 0.05, **p < 0.01, ***p < 0.001 vs. vehicle group. Degradation of glabridin and HSG4112 was measured by HPLC in f acidic solution (1% HCl in MeOH) and in g basic solution (1% NaOH in MeOH). Data represent mean ± SD; error bar is not visible because of negligible deviance. Student’s t test was performed; ***p < 0.001 vs. glabridin.